Introduction The adequate protection provided by the del Nido cardioplegia has already been proven in trials comparing the solution with blood cardioplegia. However, evidence regarding comparison to the Bretschneider HTK solution is limited. Aim To determine the efficacy of the del Nido cardioplegia when compared to Bretschneider HTK solution in patients undergoing aortic valve replacement for severe aortic stenosis. Material and methods Ten patients undergoing isolated aortic valve replacement for severe aortic stenosis using the del Nido solution (group 1) were case-control matched to patients undergoing aortic valve replacement (AVR) using the Bretschneider solution (group 2). The observation included: cardioplegia dosage, time to cardiac arrest, cross-clamp and extracorporeal circulation time, ventricular fibrillation (VF) after removing the cross-clamp, gasometry parameters, creatinine kinase (MB isoenzyme – CK-MB) at 24 and 48 h following the surgery and troponin (high‑sensitivity troponin T – hsTnT) at 24 and 48 h. Results Patients were no different in terms of comorbidities. Higher incidence of VF occurred in group 2 (3 vs. 9, 30% vs. 90%; p = 0.02). Blood sodium measurements after removing the cross-clamp were significantly higher in group 1 (median 137.0 vs. 130.0; p = 0.0004). Biomarker release trended toward lower values in group 1, but not significantly (median troponin at 24 h: 223.1 pg/ml vs. 294.8 pg/ml; p = 0.4 and 48 h: 208.0 pg/ml vs. 242.5 pg/ml; p = 0.7, median CK-MB at 24 h: 16.6 ng/ml vs. 17.3 ng/ml; p = 0.6, and 48 h: 6.7 ng/ml vs. 5.08 ng/ml; p = 0.3). Peak creatinine trended towards lower values in group 2, but not significantly (1.35 mg/dl vs. 1.05 mg/dl; p = 0.09). Conclusions Both del Nido and Bretschneider cardioplegia provide satisfactory myocardial protection. However, del Nido cardioplegia reduces the incidence of VF after declamping the aorta. Further studies are required.